First-line anlotinib-based combination treatment for patients with advanced non-small cell lung cancer: A three arms, prospective study.

e21073 Background: Anlotinib, a multi-target tyrosine kinase inhibitor antiangiogenic drug, had been recommended by guideline for the 3 lines or more treatment of non-small cell lung cancer (NSCLC) in China. However, data of anlotinib based combination in the first-line treatment remains unknown. Therefore, this study aims to evaluate efficacy and safety of the combination of erlotinib, chemotherapy or sintilimab with anlotinib respectively, in Chinese patients with locally advanced or metastatic NSCLC. Methods: In this open-label, three arms, prospective study, locally advanced or metastatic NSCLC patients with EGFR mutation (exon 19 deletion or L858R) (Cohort A) receive anlotinib (10 mg QD from day 1 to 14 of a 21-day cycle) and erlotinib (150 mg once daily) until disease progression or treatment intolerance. For patients with EGFR mutation negative, the treatment regimen was anlotinib (12 mg QD from day 1 to 14 of a 21-day cycle) in combination with chemotherapy (Cohort B) or sintilimab (Cohort C) according to investigator. The primary outcome was objective response (ORR), the secondary outcomes were progression free survival (PFS), disease control rate (DCR), overall survival (OS) and safety. Results: A total of 80 patients were enrolled with 30 patients in Cohort A, 28 patients in Cohort B, and 22 patients in Cohort C. Among these patients, 16 (57.1%), 7 (23.3%) and 1(4.5%) were female in Cohort A, B, and C, respectively. And 9 (32.1%) and 4 (18.2%) of them had brain metastasis in Cohort A and C, respectively. Till December 2020, all the patients received tumor assessment at least once. In Cohort A, 26 patients achieved confirmed PR, the ORR was 92.9%, and DCR was 96.4%. Median PFS was 20.53 months, and the 12-month PFS rate was 81.5%. In Cohort B, 17 patients achieved PR, the ORR was 60.0%, while DCR was 96.7%. Median PFS was 13.3 months, and the 12-month PFS rate was 55.5%. In Cohort C, medium PFS was 15.6 months. The 18- and 24-month PFS rate was 45.9% and 26.2%, respectively. The most common grade 3 adverse events (AEs) were rash (17.2%), oral mucositis (10.3%), diarrhea (6.9%) and proteinuria (6.9%) in Cohort A, and a grade 4 hypertension was observed. In Cohort B, the most common grade 3 AEs were platelet count decreased (20.0%), leucopenia (16.7%), hand-foot-skin reaction (10.0%), hypertriglyceridemia (10.0%), oral mucositis (6.7%) and thrombus (6.7%). Grade 4 platelet count decreased occurred in three patients (10.0%). Safety data of Cohort C had been published elsewhere. Conclusions: This study suggest that anlotinib-based combination treatment for patients with advanced non-small cell lung cancer might be new first-line therapy strategy. For EGFR-mutated positive patients, anlotinib plus erlotinib shows good efficacy and well tolerability. For EGFR-mutated negative patients, anlotinib combines with chemotherapy or sintilimab also may be a promising first-line treatment. Clinical trial information: NCT03628521.